ProMIS uses its proprietary discovery engine, consisting of two complementary algorithms, ProMIS™ and Collective Coordinates, to identify specific targets on toxic oligomers that are known root causes of neurodegenerative diseases. Such oligomers (misfolded proteins) are directly toxic to neurons and spread (propagate) in the brain or spinal cord, killing billions more neurons and leading to neurodegenerative diseases.

ProMIS has developed a rigorous screening and validation process to select the best in class product candidates to develop among our emerging portfolio of precision therapeutics. The process starts with the identification of specific targets (epitopes) on the toxic oligomers. Murine monoclonal antibodies (mAbs) are raised against these targets and evaluated in a 3-step process, to identify the best products to take into clinical development.

Initial Screening for Binding. This phase allows to identify mAbs that bind uniquely and specifically to the toxic oligomers driving Alzheimer’s disease (amyloid beta oligomers, or AβO, and Tau), Amyotrophic lateral sclerosis or ALS (SOD1 and TDP43) and Parkinson’s disease (alpha synuclein). The top candidate products, showing selective binding to the toxic oligomers and no binding to the non-toxic forms of the relevant protein, are selected for the validation phase in human tissue.

Functional Assays. Two complementary assays are used to identify, among the validated product candidates, those that demonstrate blocking of neurotoxicity (blocking the killing of neurons, a hallmark of disease) and inhibition of propagation (spreading throughout the brain)  (also a hallmark of disease). Validated product candidates meeting these criteria then undergo final testing to confirm that they block neurotoxicity in a relevant animal model.

Final validation and selection of lead product candidate for clinical development. This essential final step is accomplished by evaluating the binding of the antibody candidates to the suspected toxic oligomers from post mortem brain samples obtained from patients. For Alzheimer’s disease, lead product candidate PMN310, selectively targeting amyloid beta toxic oligomers (AβO), showed significantly greater binding to the oligomeric brain samples compared to other amyloid-directed antibody therapeutics currently in clinical development.